The research objectives of CSORDA are to gain insights into the mechanisms of action of opioid drugs at their cognate receptors with the goal of discerning molecular and cellular processes that contribute to opioid-induced behaviors as well as adaptations leading to opioid addiction, tolerance and withdrawal. The Center has six integrated components, which will investigate the activity of opioid ligands at the molecular, cellular and behavioral levels utilizing overlapping methodologies and resources. The Components of the Center will specifically investigate: I) Constitutive activity of opioid receptors as a potential target for the development of therapeutic drugs. II) Differential signaling among opioids and targeting of ligands to selective signaling pathways. III) Mechanisms of mu/delta-opioid receptor interactions that influence cellular signaling. IV) Desensitization of opioid signaling in dorsal root ganglia. V) The endogenous, opioid system as a regulator of hedonic homeostasis. VI) The role of memory and fear in opioid adaptive responses. In addition to the research specified within the components, a Pilot Program will be implemented to create new avenues of investigation within the Center and enrich the ongoing programs. For facilitation of the component and pilot programs, the Center has an Administrative Core and three Scientific Cores, which serve to integrate resources, as well as provide practical expertise and training in specific technical areas. The Scientific Cores cover molecular biology, tissue culture, mutant animal breeding/genotyping and various neurochemical procedures. Continued application of this multidisciplinary and collaborative approach will enhance our understanding of the molecular mechanisms underlying opioid actions and provide a basis for improved opioid pharmacotherapies as well as clinical approaches to ameliorating problems associated with drugs of abuse.